Research on acetaminophen as a cause of autism—updated
What evidence do we have about a causal relationship between "Tylenol" and autism?
US President Donald J. Trump announced recommendations about the use of acetaminophen (marketed under the brand name Tylenol): “If you’re pregnant, don’t take it. And don’t give it to the baby after the baby is born”
Why would President Trump (with the support of Secretary of Health and Human Services, Robert F. Kennedy, Jr., and other administration officials, some of whom are physicians) make such a specific recommendation?
They said their recommendations are based on research. So, here are links to several studies and their abstracts that have examined the question.
Alemany, S., Avella-Garcia, C., Liew, Z., Garcia-Esteban, R., Inoue, K., Cadman, T., López-Vicente, M., González, L., Galán, I. R., Andiarena, A., Casas, M., Margetaki, K., Strandberg-Larsen, K., Lawlor, D. A., El Marroun, Tiemeier, H., Iñiguez, C., Tardón, A., Santa-Marina, L., Júlvez, J., Porta, D., Chatzi, L., & Sunyer, J. (2021). Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts. European Journal of Epidemiology, 36(10), 993-1004.
The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother–child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4–12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07–1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07–1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.
Ahlqvist, V. H., Sjöqvist, H., Dalman, C., Karlsson, H., Stephansson, O., Johansson, S., Manusson, C., Gardner, R. M., & Lee, B. K. (2024). Acetaminophen use during pregnancy and children’s risk of autism, ADHD, and intellectual disability. Journal of the American Medical Association, 331(14), 1205-1214. https://doi.org/10.1001/jama.2024.3172
Importance Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy.
Objective To examine the associations of acetaminophen use during pregnancy with children’s risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.
Design, Setting, and Participants This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021.
Exposure Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records.
Main Outcomes and Measures Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers.
Results In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, −0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, −0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, −0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, −0.02% [95% CI, −0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, −0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively.
Conclusions and Relevance Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.
Damkier, P., Gram, E. B., Ceulemans, M., Panchaud, A., Cleary, B., Chambers, C., Weber-Schoendorfer, C., Kennedy, D., Hodson, K., Grant, K., Diav-Citrin, O., Običan, S. G,m Shechtman S., & Alwan, S. (2025). Acetaminophen in pregnancy and attention-deficit and hyperactivity disorder and autism spectrum disorder. Obstetrics & Gynecology, 145(2), 168-176. https://doi.org/10.1097/AOG.0000000000005802
Acetaminophen is a common over-the-counter medication that recently gained substantial media attention regarding its use by pregnant individuals. In this clinical perspective, we discuss the strengths and limitations of the published literature on the effect of maternal acetaminophen use in pregnancy on the child's risk of developing attention-deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Studies included were specifically selected on the basis of the quality and validity of ADHD or ASD outcome definitions. From a total of 56 identified studies, commentaries, and editorials of relevance, we critically reviewed nine studies with original data that satisfied our inclusion criteria and three meta-analyses. Most studies that have reported positive findings are difficult to interpret because they have important biases, notably a high degree of selection bias, variability in selection and adjustment for various potential confounders, and unmeasured familial confounding. When unobserved familial confounding through sibling analysis was controlled for, associations weakened substantially. This suggests that residual confounding from shared genetic and environmental factors may have caused an upward bias in the original observations. According to the current scientific evidence, in utero exposure to acetaminophen is unlikely to confer a clinically important increased risk of childhood ADHD or ASD. The current level of evidence does not warrant changes to clinical guidelines on the treatment of fever or pain in pregnancy. Prospective research designed to account for familial and psychosocial environmental factors related to both maternal use of acetaminophen and children's neurodevelopment should be undertaken.
Godoi, D. C., Amorim, K. G., de Oliveira Galvão, R. G., Vieira, A. P., da Costa Kotecki, L. B. C., da Hora, D. A. B., & de Souza Júnior, S. A. (2025). Association of prenatal acetaminophen exposure with risk of adhd and asd in offspring: A systematic review and meta-analysis. European Psychiatry, 68(S1), S140-S141.
Introduction: The association between prenatal acetaminophen exposure and the development of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) remains a subject of considerable debate. Despite extensive research, the evidence regarding this relationship is conflicting.
Objectives: To perform a systematic review and meta-analysis of studies comparing the incidence of ADHD and ASD in patients that were either exposed or not exposed to acetaminophen prenatally.
Methods: We systematically searched Pubmed, Embase and Cochrane Central for eligible studies up until August 2024. Only studies which included participants with a medical diagnosis of ADHD/ASD and reported acetaminophen exposure as a binary measure were included. Available summary data was extracted from published reports and pooled with a random-effects model using odds ratios (OR) with 95% confidence intervals (CI). Hazard ratios (HR) adjusted for potential confounding factors were used for sensitivity analyses. All statistical analyses were conducted utilizing Review Manager 5.4.1. PROSPERO iD:CRD42024587662.
Results: We included five studies with a total of 2,647,536 patients with ADHD (150,741) / ASD (63,726), of whom 271,126 were exposed to acetaminophen prenatally and 2,376,410 were not exposed. Prenatal acetaminophen exposure was associated with an increased risk of developing ADHD (OR 1.30; 95% CI 1.17 to 1.45; p<0.01; I2 = 73%; Figure 1) and ASD (OR 1.17; 95% CI 1.14 - 1.20; p<0.01; I2 = 0%; Figure 2). Sensitivity analyses revealed that acetaminophen exposure during the third trimester of pregnancy was associated with an increased risk of ADHD (HR 1.26; 95% CI 1.07 to 1.47; p<0.01; I2 = 0%; Figure 3), but not during first (HR 1.10; 95% CI 0.97 to 1.26; p=0.13; I2 = 0%; Figure 3) and second (HR 1.07; 95% CI 0.95 to 1.19; p=0.26; I2 = 0%; Figure 3) trimesters.
Ji, Y., Azuine, R. E., Zhang, Y., Hou, W., Hong, X., Wang, G., Riley, A, Pearson, C., Zuckerman, B., & Wang, X. (2020). Association of cord plasma biomarkers of in utero acetaminophen exposure with risk of attention-deficit/hyperactivity disorder and autism spectrum disorder in childhood. JAMA Psychiatry, 77(2), 180-189. https://doi.org/10.1001/jamapsychiatry.2019.3259
Importance Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report.
Objective To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood.
Design, Setting, and Participants This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018.
Exposures Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth.
Main Outcomes and Measures Physician-diagnosed ADHD, ASD, and other DDs as documented in the child’s medical records.
Results Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD.
Conclusions and Relevance Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.
Khan, F. Y., Kabiraj, G., Ahmed, M. A., Adam, M., Mannuru, S. P., Ramesh, V., ... & Khan, S. (2022). A systematic review of the link between autism spectrum disorder and acetaminophen: a mystery to resolve. Cureus, 14(7).
The purpose of this study is to review the published papers investigating maternal acetaminophen (AP) use during pregnancy and its effect on the offspring's neurodevelopment, particularly autism spectrum disorders (ASD). Acetaminophen is an over-the-counter analgesic and antipyretic considered safe in pregnancy. Recent studies have found an association between acetaminophen and immune system alterations like asthma and adverse neurodevelopmental outcomes. We used online databases (PubMed/Medline/PubMed Central, Science Direct, and Google Scholar) to search the studies relevant to our topic. We screened the papers by titles, abstracts, and then full-text availability. The screened articles were checked for eligibility using relevant quality assessment tools for each study design, extracting and analyzing the data. We finalized 30 studies after the screening; 14 were ineligible. Our final selection included 16 high-quality papers - 13 prospective cohort studies, two review articles, and one meta-analysis.
We found a wide range of neurodevelopmental outcomes in our data collection. So, we included autism spectrum disorders, intelligent quotient (IQ), attention-deficit/hyperactivity disorder (ADHD), isolated language, attention and executive function, communication, behavior, and psychomotor development. All studies showed an association between acetaminophen use and listed neurodevelopmental outcomes. Long-term use, increased dose, and frequency were associated with a stronger association. We extracted collective evidence from 16 studies suggesting acetaminophen's role in developing adverse neurodevelopmental outcomes. It is urgent to do more research on this association before pregnant women can be cautioned about the precise use of acetaminophen.
Masarwa, R., Levine, H., Gorelik, E., Reif, S., Perlman, A., & Matok, I. (2018). Prenatal exposure to acetaminophen and risk for attention deficit hyperactivity disorder and autistic spectrum disorder: a systematic review, meta-analysis, and meta-regression analysis of cohort studies. American Journal of Epidemiology, 187(8), 1817-1827. [Also see https://doi.org/10.1093/aje/kwy202
Acetaminophen is the analgesic and antipyretic most commonly used during pregnancy. Evidence of neurodisruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention de cit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, Embase, and Cochrane databases for relevant studies up to January 2017. Data were independently extracted and assessed by 2 researchers. Seven eligible retrospective cohorts included 132,738 mother-child pairs, with follow-up periods ranging from 3 to 11 years. The pooled risk ratio for ADHD was 1.34 (95% con dence interval (CI): 1.21, 1.47; I2 = 72%); for ASD, the risk ratio was 1.19 (95% CI: 1.14, 1.25; I2 = 14%), and for hyperactivity symptoms, it was 1.24 (95% CI: 1.04, 1.43; I2 = 93%). In meta-regression analysis, the association between exposure and ADHD increased with the child’s age upon follow-up (β= 0.03, 95% CI: 0.00, 0.07) and with the mean duration of exposure (β= 0.00, 95% CI: 0.00, 0.01). The available data is of observational nature only. Studies differed widely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD, and hyperactivity symptoms. These ndings are concerning; however, results should be interpreted with caution given that the available evidence consists of observational studies and is susceptible to several potential sources of bias.
Prada, D., Ritz, B., Bauer, A. Z., & Baccarelli, A. A. (2025). Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environmental Health, 24(1), 56. https://doi.org/10.1186/s12940-025-01208-0
Background Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed studies have indicated that pregnant mothers exposed to acetaminophen have children diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), at higher rates than children of pregnant mothers who were not exposed to acetaminophen.
Methods We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide’s focus on environmental health evidence. Results We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis.
Conclusions Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring’s neurodevelopment.
Ricci, C., Albanese, C. M., Pablo, L. A., Li, J., Fatima, M., Barrett, K., Levis, B., & Brown, H. K. (2023). In utero acetaminophen exposure and child neurodevelopmental outcomes: systematic review and meta‐analysis. Paediatric and Perinatal Epidemiology, 37(5), 473-484. https://doi.org/10.1111/ppe.12963
Background: Acetaminophen is a frequently used analgesic for pain and fever. There have been reports of adverse neurodevelopmental outcomes associated with in utero acetaminophen exposure. However, it is unclear whether this association is related directly to acetaminophen use, or the reasons for use.
Objectives: To summarise the literature on the association between in utero acetaminophen exposure and child neurodevelopmental outcomes, and assess the extent to which the association is due to confounding by indication.
Data Sources: OVID for Medline, Embase, and PsycINFO, and EBSCO for CINAHL, from inception to August 18, 2022.
Study Selection and Data Extraction: We searched for peer- reviewed, English-language studies on in utero acetaminophen exposure and child neurodevelopmental outcomes. Data were extracted using a standardised form created a priori, and quality was assessed using the Systematic Assessment of Quality in Observational Research.
Synthesis: We generated pooled risk ratios (RR) for outcomes examined by ≥3 studies using random- effects models; outcomes that could not be meta-analysed were narratively summarised following Synthesis Without Meta- Analysis guidelines.
Results: Twenty-two studies including 23 cohorts were eligible (n = 367,775 total participants; median: 51.7% with acetaminophen exposure). Studies were primarily prospective cohort studies from Europe and the US, with attention deficit/hyperactivity disorder (ADHD) being the most common outcome. Quality assessments resulted in 13.6% of studies being classified as high, 59.1% as medium, 22.7% as low, and 4.5% as very low quality. In utero acetaminophen exposure was associated with an ele- vated risk of ADHD (unadjusted pooled RR 1.32, 95% confidence interval [CI] 1.20, 1.44; I2 = 47%, n = 7 studies), with little difference after adjusting for confounders, including indications for acetaminophen use (adjusted pooled RR 1.34, 95% CI 1.15, 1.55; I2 = 50%, n = 4 studies).
Conclusions: Confounding by indication did not explain the association between in utero acetaminophen exposure and child ADHD. Further, high- quality research is needed on this and other neurodevelopmental outcomes.
Here’s an image from the press conference:
This is an update to the an earlier version of the post under a similar title. The main change is that I added a half dozen more citations and abstracts. I copied the original and can provide a PDF of it.